Abstract

BackgroundA key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni.MethodsWe examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel.ResultsPrevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment.ConclusionsOur findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow.

Highlights

  • A key component of schistosomiasis control is mass drug administration with praziquantel

  • Faust et al Parasites Vectors (2019) 12:607 reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme

  • These results suggest that mass drug administration (MDA) in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow

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Summary

Introduction

A key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Adult Schistosoma mansoni sexually reproduces (predominantly) in humans and eggs are excreted in faeces. Worm burdens can be very heavy, producing as many as 9600 eggs per gram (epg) of stool [2]. In areas with inadequate containment of stool due to poor sanitation, eggs contact freshwater and hatch into freeswimming miracidia. Despite the integral role of insufficient water, sanitation and hygiene (WASH) in maintaining transmission, preventative chemotherapy through mass drug administration (MDA) with praziquantel is currently the main strategy for controlling morbidity, and transmission, of schistosomiasis in endemic areas [4]. While MDA has been successful in reducing morbidity and prevalence or intensity of schistosomiasis across many parts of sub-Saharan Africa [5,6,7], persistent transmission hotspots of Schistosoma species remain [8, 9]

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